Browsing by Subject "FAMILY"

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Open Access
Analysis of enriched rare variants in JPH2-encoded junctophilin-2 among Greater Middle Eastern individuals reveals a novel homozygous variant associated with neonatal dilated cardiomyopathy.
(Scientific reports, 2019-06-21) Jones, Edward G; Mazaheri, Neda; Maroofian, Reza; Zamani, Mina; Seifi, Tahereh; Sedaghat, Alireza; Shariati, Gholamreza; Jamshidi, Yalda; Allen, Hugh D; Wehrens, Xander HT; Galehdari, Hamid; Landstrom, Andrew P
Junctophilin-2 (JPH2) is a part of the junctional membrane complex that facilitates calcium-handling in the cardiomyocyte. Previously, missense variants in JPH2 have been linked to hypertrophic cardiomyopathy; however, pathogenic "loss of function" (LOF) variants have not been described. Family-based genetic analysis of GME individuals with cardiomyopathic disease identified an Iranian patient with dilated cardiomyopathy (DCM) as a carrier of a novel, homozygous single nucleotide insertion in JPH2 resulting in a stop codon (JPH2-p.E641*). A second Iranian family with consanguineous parents hosting an identical heterozygous variant had 2 children die in childhood from cardiac failure. To characterize ethnicity-dependent genetic variability in JPH2 and to identify homozygous JPH2 variants associated with cardiac disease, we identified variants in JPH2 in a worldwide control cohort (gnomAD) and 2 similar cohorts from the Greater Middle East (GME Variome, Iranome). These were compared against ethnicity-matched clinical whole exome sequencing (WES) referral tests and a case cohort of individuals with hypertrophic cardiomyopathy (HCM) based on comprehensive review of the literature. Worldwide, 1.45% of healthy individuals hosted a rare JPH2 variant with a significantly higher proportion among GME individuals (4.45%); LOF variants were rare overall (0.04%) yet were most prevalent in GME (0.21%). The increased prevalence of LOF variants in GME individuals was corroborated among region-specific, clinical WES cohorts. In conclusion, we report ethnic-specific differences in JPH2 rare variants, with GME individuals being at higher risk of hosting homozygous LOF variants. This conclusion is supported by the identification of a novel JPH2 LOF variant confirmed by segregation analysis resulting in autosomal recessive pediatric DCM due to presumptive JPH2 truncation.
Open Access
The Household as a Source of Labor for Entrepreneurs: Evidence from New York City during Industrialization
(Strategic Entrepreneurship Journal, 2020) Ruef, M
Research Summary: This article conceptualizes households as a crucial pool of labor for small entrepreneurs. The household varied historically in its scope (depending on whether bonded workers were included) and work intensity (depending on the authority or coercion exercised by household heads). Drawing on data that enumerate over 100,000 households in New York City, I examine how the shift from institutions of unfree labor to wage labor affected business proprietorship between 1790 and 1850. Given the disproportionate importance of unfree household labor to small entrepreneurs, the contraction of this labor source may offer one general explanation for their decline. Managerial Summary: How does household scope and composition affect the ability of an individual to run their own business? Historical archives can provide useful insights into this question. They track long-term declines in family size and the emancipation of non-family members—such as apprentices, indentured servants, and slaves—from the authority of household heads. Examining records from early New York City, this study shows that business ownership was strongly linked with the ownership of slaves and the presence of dependent males after the American Revolution. Large households and unfree laborers were especially important for entrepreneurship among individuals with limited wealth. For modern economies, the results suggest that policymakers consider potential tensions between small business ownership and the development of free and equitable labor markets.